Z -thienyl



Patented Aug. 7, 1951 UNITED STATES PATENT OFFICE 4- (2'-THIENYL) -2-MERCAPTOTHIAZOLES William S. Emerson and Tracy M. Patrick, Jr., Dayton, Ohio, assignors to Monsanto Chemical Company, St. Louis, Mo., a corporation of Delaware No Drawing. Application August 27, 1947, Serial No. 770,958

8 Claims. (Cl. 260-302) The present invention relates to 4-(2-thienyl) 2-mercaptothiazoles and derivatives thereof and to their preparation. By 4-(2'-thienyl)-2-mercaptothiazole is meant a compound of the structure 5 where R is a Z-thienyl group as for example a invention is R-O-N l: I]: \0S]M where R is a Z-thienyl group and M is hydrogen, a salt forming group, an ester forming group, an ether forming group or the group in parentheses. Typical examples of salt forming groups are NH4-, CsH11NH3-, (C2H5) 2NH2-, (CH3) 2NH2--,

CH2-- OE:

(CH2)5NH2, Na, K, Zn, Pb, Sn, Mg, Hg, and Ca. By ester forming groups are meant acyl and aroyl groups examples of which are 2 CI EL By ether forming groups are meant mono-substituted methyl groups resulting in the formation of compounds in which the sulfur atom is attached to a methylene group. Typical examples of ether forming groups are ina gum O1@E OH.

and

and the like.

Disulfides of 4-(2'-thienyl)-2-mereaptothiazoles are readily obtained by oxidation of the corresponding mercaptans with hydrogen peroxide, sodium hypochlorite, chlorine or other oxidizing agent.

The synthesis of Z-mercaptothiazoles substituted in the 4-position by an aromatic group has been effected by reacting'phenacyl bromide with ammonium dithiocarbamate. For instance, Miolati, Gazz. chim. ital. 23 (l), 575 (1893) got 4-phenyl-2-mercaptothiazole from phenacyl bromide and ammonium dithiocarbamate by heating in alcoholic solution. Levi, Gazz. chim. ital, 61, 719 (1931) treated phenacyl bromide with ammonium dithiocarbamate in ether to obtain phenacyl dithiourethane which cyclized on heating above its melting point to 4-phenyl-2-mercaptothiazole. Similarly, Ubaldini and Fiorenza, Gazz. chim. ita1., 73, 169-175 (1943) obtained phenacyl dithiourethane and 4-pheny1-2-thiazyl phenacyl thioether from equimolecular amounts of phenacyl bromide and ammonium dithiocarbamate.

From equimolar portions after 16 hours they got 55% of 4-phenyl2-mercaptothiazole and 45% of the thioether. When the molar ratio of phenacyl bromide and ammonium dithiocarbamate was 2:1, they got 100% of the thioether after 16 hours.

The mercaptothiazole reacted with phen acyl bromide in ether to yield the hydrobromide of the thioether. Also, the dithiourethane and phenacyl bromide yielded the thioether.

While the 4-thienyl-2-mercaptcthiazoles may be prepared in analogous manner. namely by reaction of w-bromoacetothienone and ammonium dithiocarbamate, very much better results are obtained by reacting w-chloroacetc'thienone and a dithiocarbamate. Bromides are frequently preferred to chlorides in organic synthesis because of their greater reactivity but the increased reactivity has in this instance been found to be a disadvantage.

The following are specific embodiments of the invention which are to be taken as illustrative but not llmitative thereof.

EXAMPLE I A mixture of 120.3 g. 0.75 mole) of w-chlorostoppered and allowed to stand at room temperature for four dayswith occasional shaking. The slurry of crystals was then diluted with 200 ml. of water and filtered. The residue was washed thoroughly with water, and then treated with 125 m1.

of 5% aqueous sodium hydroxide in-f the cold.

The solid was nearly all soluble. The-resulting mixture was filtered and the filtrate was cart acetothienone, 82.5 g. (0.75 mole) of ammonium dithiocarbamate, and 600 ml. of anhydrous ether 7 was placed in a 1500 ml. Erlenmeyer flask cooled by an ice bath. The flask was stoppered and shaken occasionally. Afterone-hali hour the ice 1 bath was removed and the flask was allowed to stand at room temperature for fifteen days'with occasional shaking. The mixture now consisted of yellow crystals in ether suspension. The crystals were removed by filtration and treated with 1 liter of cold 5% sodium hydroxide solution. Most of the solid dissolved, The resulting suspension was filtered and the filtrate made acid with 10% hydrochloric acid, causing a yellow-tan precipitate of crude 4--(2 -thienyl)-2-mercaptothiazole toform. She product was removed byv filtration, washed with water, and dried. It weighed 74.1 g. and melted at 176-l77 C. (con) The ether filtrate from above was washed three times with water, and then extracted with EXAMPLE "II The alkali insoluble material from Example I obtained from the original separation of the yel low crystals from the ether suspension (8.0g)

melted at 86-88 C. (cor.). This was identified as the thienacyl thioether of 4-(2'-thienyl)-2-mercaptothiazole.

An analytical sample of the thienacyl thioether of 4-(2'-thienyl)-2 mercapt0thiazole, obtained by recrystallization from ethanol, melted at 89-'-90 C. (cor.). Anal: Calculated for Ci3H9ONS4: 'N, 4.33%; S, 39.66%. Found: N,

EXAMPLE III A mixture of 161.1 g. of w-chloroacetothienone, 16.5 g. of ammonium dithiocarbamate and 150' mlof absolute ethanol was shaken during cooling in an ice bath for thirty minutes. The flask was A second crop fully acidified with dilute hydrochloric acid. Crude '4- (2-thienyl) -2-mercaptothiazole precipitated. It was removed by filtration, washed. and dried. It weighed 17.2 g.'(86% yield), and

melted at 173-1.76 C. (cor.).

EXAMPLE iv e To an ice cold solution of 16.5 g. of ammonium dithiocarbamate in 200 ml. of water there was added gradually with shaking 16.1 g. of w-ChlOI'O- acetothienone. The flask was stoppered and the mixture was allowed to stand at room temperature with occasional shaking for four days. The yellow solid product, was removed by filtration, washed thoroughly with water, and dried. It was then added to 200 m1. of dry benzene an'dthe mixture was refluxed two hours under a Stark and Dean trap. The benzene was then evaporated. The residue was treated simultaneously with 150 ml. of 5% aqueous sodium hydroxide and ml. of benzene' The resulting immiscible solutions were separated, and the benzenesolution was extracted once with 15 mlrof aqueous sodium hydroxide. The alkaline solutions-were combined, cooled, and acidified with dilute hydrochloric acid. The crude 4-(2'thienyl)-2- mercaptothiazole thus precipitated weighed 12.4 g. (62% yield) and melted at 17l176 C. (cor.).

EXAMPLE V A mixture of 39.0 g. of 5,w-dichloro-2-aceto thienone and 33.0 g. of ammonium dithiocar bamate in 250 ml. of anhydrous ether was thor oughly shaken and then allowed to stand at room temperature for four days with occasionalshak- EXAMPLE v1 The crude alkali-insoluble 4-(5-chloro- 2' thienyl)-2-thiazyl 5-chloro-2-thienacyl thioether from Example V was purified by recrystallization irom benzene. It melted at l33-134 C. (cor.). Cl, 18.07%. Found: S, 32.65%; Cl, 17.62%.

EXAMPLE VII A mixture of 19.5 g. '5,wdlChl010-2-8.C6t0- thienone and 16.5 g. of ammonium dithiocarbamate in m1. of absolute ethanol was shaken While cooling in an ice bath for five minutes. The mixture was then allowed to stand at room temperature for seven dayslwith occasional shak- Found: S,

Calculated for C'13H7ONS4C12Z S, 32.70%; s

ing. It was then diluted with 150 ml. of water, cooled, and filtered. The residue was washed thoroughly with water, and then treated with 175 ml. of 10% aqueous potassium hydroxide. Nearly all the solid dissolved. The alkaline mixture was filtered, and the filtrate was cooled and acidified with dilute hydrochloric acid. The precipitated crude 4-(5'-chloro-2'-thienyl)-2-mercaptothiazole, after washing and drying, weighed 20.7 g. (91% yield) and melted with decomposition at 201 C. (con).

Products of this invention are valuable accelerators of vulcanization. It is significant that the presence of a thienyl group on the thiazole nucleus enhances the accelerating activity, a thienyl group being more effective for this purpose than a phenyl group. As illustrative of the accelerating properties, stocks were compounded comp isin Stock A B Parts by Paris by weight weight Pale crepe rubber. 100 100 inc oxide 5 5 Btearic acid l 1 Sulfur 3 3 4-(2-thienyl)-2-mercaptothiazole 1 d-Phenyl-2-mercaptothiazo1e 1 The stocks so compounded were cured by heating in a press in the usual manner for different periods of time at 126 C. The physical properties of the cured rubber products are set forth below:

Table Modulus of Elasticity in lbs/in. mt Cure at Elongations Tensile at E1 Stock Time, in of- Break, in

mins. lbs./i11. 55,

15 401 l, 270 2, 641 825 15 301 918 l, 987 830 30 488 2, 298 3, 262 760 30 445 l, 784 2, 370 775 45 652 2, 967 3, 472 740 45 592 2, 420 2, 433 705 of the group consisting of hydrogen, salt forming groups and O-SM o -CHa- -R groups.

2. A compound of the structure CHCH Brg-C-N s c sn 3. A compound of the structure CHOE t c N s o-sn H -s a 4. A compound of the structure CH-OH (3H c t-o-N s C-SH 5. A compound of the structure CH-CH t c N s c-sn 6. The method of making a 2-mercaptothiazole substituted in the -position by a thienyl group which comprises reacting a salt of dithiocarbamic acid with a chloride of the structure Where T represents a Z-thienyl group in a solvent.

8. The method of making a Z-mercaptothiazole substituted in the 4-position by a thienyl group which comprises reacting ammonium di thiocarbamate with w-chloroacetothienone in a. solvent.

WILLIAM S. EMERSON.

TRACY M. PATRICK, JR.

While the invention has been illustrated by reference to a number of specific embodiments of the invention, it will be apparent that many variations may be made from the specific procedures described and from the particular compounds, reacting ingredients, compounding ingredients and solvents specifically enumerated.

This invention is limited solely by the claims attached hereto as part of the present speciflcation.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,186,421 Mathes Jan. 9, 1940 2,196,607 Mathes Apr. 9, 1940 2,304,112 Middleton Dec. 8, 1942 

1. A COMPOUND OF THE STRUCTURE 